It is proposed to test whether a series of cocarcinogen derivatives known to cause a graded biological response also has a graded effect upon structural or functional properties of cellular organelle membranes. We will continue our examination of the effects of cocarcinogens such as lipophilic phorbol esters upon membrane transport by plasma cell membranes. Specifically, it is proposed to test the influence of cocarcinogens on changes in monovalent cation movements. Attempts will be made to examine the nature of the effect of cocarcinogens on several enzymes involved in membrane transport and catalytic function, e.g., (Na plus K ions)-ATPase, adenyl cyclase. The basis for TPA inhibition of (Na plus K ions)-ATPase will be examined further to determine whether this is the result of TPA's effect on the lipid component of ATPase or on the protein itself. Fluorescent probes will be used in model systems as phospholipid bilayers to learn whether the membrane interface is altered by TPA.